Association of Oral Microbiome With Oral Human Papillomavirus Infection: A Population Study of the National Health and Nutrition Examination Survey, 2009–2012

Abstract Background Oral human papillomavirus (HPV) infection and the oral microbiome are associated with oropharyngeal cancer. However, population-based data on the association of oral microbiome with oral HPV infection are limited. Method A cross-sectional analysis of 5496 20–59-year-old participants in the 2009–2012 National Health and Nutrition Examination Survey was performed. Associations with oral HPV infection were assessed using multivariable logistic regression for oral microbiome α-diversity (within-sample diversity), and using principal coordinate analysis and permutational multivariate analysis of variance for β-diversity (between-sample heterogeneity). Results Overall, for α-diversity, a lower number of observed amplicon sequence variants (adjusted odds ratio [aOR] = 0.996; 95% confidence interval [CI] = .992–.999) and reduced Faith's phylogenetic diversity (aOR = 0.95; 95% CI = .90–.99) were associated with high-risk oral HPV infection. β-diversity showed differentiation of oral microbiome community by high-risk oral HPV infection as measured by Bray-Curtis dissimilarity (R2 = 0.054%; P = .029) and unweighted UniFrac distance (R2 = 0.046%; P = .045). There were differential associations when stratified by sex. Conclusions Both oral microbiome α-diversity and β-diversity were marginally associated with oral HPV infection. Longitudinal studies are needed to characterize the role of the microbiome in the natural history of oral HPV infection.